CBX3/HP1γ promotes tumor proliferation and predicts poor survival in hepatocellular carcinoma.

Xiaoping Zhong,Huayong Zhang,Wancong Zhang,Shijie Tang,Jianda Zhou,Anna Kan,Jiasheng Chen

doi:10.18632/aging.102132

Abstract

HP1γ, encoded by CBX3, is associated with cancer progression and patient prognosis. However, the prognostic value and functions of CBX3/HP1γ in hepatocellular carcinoma (HCC) remain unclear. Here, we performed a bioinformatics analysis using the Oncomine, TCGA and Human Protein Atlas databases, the Kaplan-Meier plotter, and the UALCAN web-portal to explore the expression and prognostic significance of CBX3/HP1γ in patients with different cancers, including liver cancer. HCC tissues and microarrays containing 354 samples were examined using immunohistochemical staining, quantitative real-time polymerase chain reaction, and Western blotting. CBX3-overexpression HCC cell lines were tested in proliferation assays to determine the function of CBX3/HP1γ. We found that CBX3/HP1γ was upregulated in many cancers and was associated with poor prognosis. Our results also revealed that CBX3/HP1γ is elevated in HCC tissues and is associated with malignant clinicopathological characteristics. Kaplan-Meier and Cox regression analyses verified that high CBX3/HP1γ expression is an independent and significant prognostic factor for reduced overall survival in HCC patients. Moreover, in vitro functional assays showed that CBX3/HP1γ overexpression promotes HCC cell proliferation. These findings suggest that CBX3/HP1γ is an important oncogene in HCC that might act as a useful biomarker for prognosis and targeted therapy.

Highlights

Liver cancer was the third leading cause of cancer-related mortality worldwide in 2018, and its incidence is rising, in Asia and Africa [1,2,3]
Bioinformatic analysis indicated that upregulated Chromebox protein homolog 3 (CBX3)/Heterochromatin protein 1 gamma (HP1γ) expression predicts poor prognosis in liver cancer (Figure 1C), breast cancer (Figure 1D), pancreatic cancer (Figure 1E), and renal cancer (Figure 1F) (Kaplan-Meier plot, log-rank test, all P values< 0.001)
The results showed that CBX3/HP1γ interacts with CBX1 and CBX5, which are members of the heterochromatin protein 1 family

Summary

Introduction

Liver cancer was the third leading cause of cancer-related mortality worldwide in 2018, and its incidence is rising, in Asia and Africa [1,2,3]. Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers, and prognoses remain poor for HCC patients because of the high likelihood of metastasis and recurrence [4, 5]. This low long-term survival rate is most likely attributable to the biological behavior of cancer cells [6, 7]. CBX3/HP1γ expression and its impact on clinical pathologic parameters have not been studied in HCC patients

Methods

Results

Conclusion